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Background Rapid blood culture diagnostics are of unclear benefit for patients with gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, randomized, controlled trial comparing outcomes of patients with GNB BSIs who had blood culture testing with standard-of-care (SOC) culture and antimicrobial susceptibility testing (AST) vs rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno System (RAPID). Methods Patients with positive blood cultures with Gram stains showing GNB were randomized to SOC testing with antimicrobial stewardship (AS) review or RAPID with AS. The primary outcome was time to first antibiotic modification within 72 hours of randomization. Results Of 500 randomized patients, 448 were included (226 SOC, 222 RAPID). Mean (standard deviation) time to results was faster for RAPID than SOC for organism ID (2.7 [1.2] vs 11.7 [10.5] hours; P Conclusions Rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for gram-negative BSIs. Clinical Trials Registration NCT03218397.

Background Although statins, angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are generally well tolerated, the impact of these therapies individually or in combination on the change in neurocognitive function in persons with human immunodeficiency virus infection is unknown. Methods The study included participants in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort participants not receiving a statin or ACEI/ARB within 30 days of first neurologic assessment (baseline), with assessments by NPZ-3 (z score of averaged Trailmaking A and B tests and digit symbol test [DST]) from ≥2 measurements. Marginal structural models estimated the causal effect of statin or ACEI/ARB initiation on neurocognitive function; initial constant slope was assumed during the first year of treatment and a second constant slope thereafter. Results Of 3949 eligible participants, 16% started therapy with a statin, 11% with an ACEI/ARB, and 5% with both. Statin therapy had no significant effect on the composite NPZ-3 (primary outcome), Trailmaking B test, or DST. A small, nonsignificant positive effect on the Trailmaking A test was seen during year 1 (estimate, 0.088; 95% confidence interval, -.010 to .187; P = .08) and a small but significant negative effect (-0.033; -.058 to -.009; P = .007) in each subsequent year. ACEI/ARB therapy had a significant negative effect on the DST (-0.117; 95% confidence interval, -.217 to .016; P = .02) during year 1 but minimal effect in subsequent years or on other neurocognitive domains. Conclusions In summary, although modest declines in neurocognitive performance were seen in single domains with statin or ACEI/ARB therapy, we did not find consistent evidence that statins or ACEI/ARB have an effect on global neurocognitive function. Future studies should focus on long-term neurocognitive effects.